title: Monitoring of nuclear factor of activated T-cell-regulated gene expression in de novo and long-term liver transplant recipients treated with cyclosporine a.
abstract: Pharmacodynamic drug monitoring might allow an improved use of immunosuppressive medication in transplant recipients. We assessed whether drug concentrations reflect the effect of cyclosporine (CsA) on expression of nuclear factor of activated T-cells-regulated cytokines. CsA drug concentrations and expression of interleukin-2, interferon-γ, and granulocyte-macrophage colony-stimulating factor in stimulated blood lymphocytes were determined predose (C0) and 2 hours after (C2) CsA intake in 20 de novo (less than 3 months) and 20 long-term (3 months to 10 years) liver transplant patients. The residual cytokine expression at C2 relative to C0 was calculated. Mean CsA C0 and C2 concentrations were 236 and 776 μg/L in de novo and 100 and 573 μg/L in long-term liver transplant patients, respectively. Two hours after CsA intake, the residual cytokine expression for all cytokines was comparable in both groups (de novo patients mean 16%; long-term patients mean 17%). CsA C2 concentrations showed a significant (P < 0.01) correlation with the residual cytokine expression of interleukin-2, interferon-γ, and granulocyte-macrophage colony-stimulating factor in both de novo and long-term patients, whereas CsA C0 concentrations did not. The data suggest that CsA C2 concentrations, but not C0 concentrations, reflect the effect of CsA on downregulation of cytokine expression in both de novo and long-term liver transplant patients.
authors.affiliation: Department of Hepatobiliary Surgery and Solid Organ Transplantation, University Medical Center Hamburg-Eppendorf, Hamburg, Germany. utaherden@gmail.com
authors.forename: Uta
authors.initials: U
authors.lastname: Herden
authors.forename: Arno
authors.initials: A
authors.lastname: Kromminga
authors.forename: Christine
authors.initials: C
authors.lastname: Hagel
authors.forename: Jürgen
authors.initials: J
authors.lastname: Hartleb
authors.forename: Björn
authors.initials: B
authors.lastname: Nashan
authors.forename: Martina
authors.initials: M
authors.lastname: Sterneck
authors.forename: Lutz
authors.initials: L
authors.lastname: Fischer
mesh_terms: D016572:Cyclosporine / Q000008:administration & dosage / Q000097:blood* / Q000378:metabolism / Q000627:therapeutic use*; D016903:Drug Monitoring; D015870:Gene Expression; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000096:biosynthesis / Q000097:blood; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage / Q000097:blood / Q000378:metabolism / Q000627:therapeutic use*; D007371:Interferon-gamma / Q000096:biosynthesis / Q000097:blood; D007376:Interleukin-2 / Q000096:biosynthesis / Q000097:blood; D016031:Liver Transplantation; D008214:Lymphocytes / Q000378:metabolism; D050778:NFATC Transcription Factors / Q000097:blood* / Q000235:genetics*; D013601:T-Lymphocytes / Q000378:metabolism; D013997:Time Factors
chemical_list: D007166:Immunosuppressive Agents; D007376:Interleukin-2; D050778:NFATC Transcription Factors; D007371:Interferon-gamma; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D016572:Cyclosporine